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Brain Scans Support Genes’ Role in Alzheimer’s Disease

By comparing genome-wide data and brain MRIs from more than 700
people, scientists have confirmed that 4 suspect genes are tied
to Alzheimer’s disease. The researchers also linked the disease
to 2 new genes, offering unexpected targets for future research.

Alzheimer's disease is an irreversible, progressive brain disease.
It starts with mild memory problems and ends with severe brain
damage. In most affected people, symptoms first appear after age
60.

Research suggests that Alzheimer's disease is up to 80% heritable,
but until recently only one gene, known as APOE, had been
linked to disease risk and age at onset. Last year, genome-wide
association studies identified 3 additional chromosome regions,
or loci, that affect Alzheimer's risk. Still, the underlying causes
of the disease remain mostly unknown.

In the new study, reported in the June 2010 issue of the Archives
of Neurology, scientists searched for connections between
gene variants and specific brain changes typical of Alzheimer's
disease. The researchers drew on publicly available data collected
for the Alzheimer's Disease Neuroimaging Initiative. This research
consortium conducts genome-wide analyses and collects neuroimaging
and other data on older adults from across North America. The
initiative is a public-private partnership funded primarily by
NIH’s National Institute on Aging (NIA) and National Institute
of Biomedical Imaging and Bioengineering (NIBIB), along with
pharmaceutical companies and other organizations.

The scientists analyzed data on 168 Alzheimer's patients, 357
people with mild cognitive impairment (a precursor to Alzheimer's
disease) and 215 who were cognitively normal. They scoured MRIs
for structural traits in 6 brain regions linked to Alzheimer's
disease, including changes in the size of the amygdala and hippocampus.

The researchers found that APOE had the strongest association
with clinical Alzheimer's disease and was linked to all the neuroimaging
traits except one. The 3 genes identified last year, along with
2 new target genes, had a significant cumulative effect on all
6 neuroimaging traits. The newly identified genes—BIN1 and CNTN5—are
known to contribute to neuron function, although their roles are
poorly understood.

"The genes we identified, and other genes that they interact
with, will provide good targets for drug development in the future," says
study coauthor Dr. Alessandro Biffi of Massachusetts General Hospital
and the Broad Institute. "Still, with the information we have,
we're not able to provide any type of personalized medicine for
Alzheimer's disease, mainly because the effects of these gene variants
are very weak."